Expression of Mucins and Cytokeratins in Primary Carcinomas of the Digestive System

Abstract

To determine the most optimal treatment of cancer patients, it is fundamental to classify human carcinomas according to their primary anatomical site of origin. As for some patients, it is difficult to identify cancers occurring at obscure location and overlapping adjacent sites. The aim of this study is to partition the primary site of 486 patients in cancers of the digestive system by the expression pattern of the mucins and cytokeratins typifying each site. The expressions of MUC1, MUC2, MUC5AC, MUC6, CK7, CK8, CK13, CK14, CK18, CK19 and CK20 were evaluated immunohistochemically in 426 adenocarcinomas and 60 hepatocellular carcinomas using the tissue-array method. The finding of MUC series showed their characteristics in case of MUC2 in the appendix cancer and MUC1 and 5AC in pancreas cancer. As for CKs 7, 13, and 19, and 20 had a feature in cancers of common bile duct, liver, and appendix, respectively. We classified cancers in 11 sites by characteristic expression of antibodies. The sensitivity, specificity, positive predictive value, and diagnostic efficacy of significant antibodies were calculated with deducing the dichotomous tree made by SPSS 10.0. Six of 11 antibodies, CK 7, CK13, CK19, CK20, MUC1, and MUC5AC distinguished 6 groups from 11 sites. We also executed the clustering of cancers to investigate total relationship among cancers. They fell into three categories, which corresponded to embryologic origin. Unlike other sites, the small intestine and colorectum cancers expressed significantly different patterns to their sublocations. Mucins and CKs showed expression patterns to classify the primary sites of digestive cancers and may be helpful in predicting the primary sites of digestive cancers.

Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

“…11,21,34,35 However, due to the small number of patients who were evaluated in these earlier reports, insufficient data were available to determine the prognostic significance of the 16,17,19 However, no significant survival differences were observed in our current small intestinal adenocarcinoma cohort in terms of MUC1 protein expression, which is different from the findings in gastric cancer. Lee et al 11 have previously reported that duodenal cancers more frequently demonstrate MUC1 protein expression (10 of 14 cases; 71%) than jejunal and ileal cancers (2 of 9 cases; 22%), but they did not report any differences in terms of MUC5AC or MUC6 expression. In contrast to this previous study, we did not find any differences in MUC1 protein expression in terms of small intestinal adenocarcinoma location in our current analyses; however, we observed MUC5AC and MUC6 expression more frequently in duodenal cancers than in distal (jejunal and ileal) cancers.…”

“…9 Among mucin proteins, MUC1, MUC5AC, and MUC6 have been investigated in various gastrointestinal organs. 11 In the normal mucosa of the gastrointestinal tract, MUC1 (also known as epithelial membrane antigen), which is located on chromosome 7q22, is mainly expressed in the pancreatic ducts and superficial foveolar epithelium. 12 MUC5AC and MUC6, which are located on chromosome 11p15, demonstrate considerably similar overall homologies.…”

“…Although a few studies have reported the expression patterns of CDX2 and mucin proteins in small intestinal adenocarcinomas and ampullary carcinomas, most of these analyses were performed on a small number of small intestinal adenocarcinoma patients. 11,13,21,[33][34][35][36][37][38] Moreover, to the best of our knowledge, no previous studies have investigated the prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinomas.…”

Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma

“…Overexpression of MUC5AC in PDA has been reported in 70% to 100% of the cases in several studies [13,14,25]. Similarly, a high frequency of MUC5AC expression has been reported in cholangiocarcinoma [11,13,14,[26][27][28][29] and gallbladder adenocarcinoma [11,15]. In the studies where ICC and extrahepatic cholangiocarcinoma (ECC) were separately evaluated, it was apparent that ECCs more frequently expressed MUC5AC than ICCs.…”

“…However, the expression characteristics of these biomarkers have not been well studied in ICC. Similarly, immunohistochemical expression of MUC5AC and cytokeratin 17 (CK17) proteins in adenocarcinomas of the pancreas, gallbladder, and bile ducts has been examined in several studies [11][12][13][14][15][16], but their use in the distinction between ICC and PDA has not been specifically investigated.…”